A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is a malignant disease containing tumor-infiltrating lymphocytes. Reactive oxygen species (ROS) are present in the tumor microenvironment and are strongly associated with cancer development. Nevertheless, the role of ROS-related genes in ccRCC remain...

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Main Authors: Hongxiang Liu, Yong Luo, Shankun Zhao, Jing Tan, Minjian Chen, Xihai Liu, Jianheng Ye, Shanghua Cai, Yulin Deng, Jinchuang Li, Huichan He, Xin Zhang, Weide Zhong
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2023.1202151/full
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author Hongxiang Liu
Hongxiang Liu
Yong Luo
Shankun Zhao
Jing Tan
Minjian Chen
Xihai Liu
Jianheng Ye
Shanghua Cai
Shanghua Cai
Yulin Deng
Jinchuang Li
Huichan He
Xin Zhang
Weide Zhong
Weide Zhong
Weide Zhong
Weide Zhong
Weide Zhong
author_facet Hongxiang Liu
Hongxiang Liu
Yong Luo
Shankun Zhao
Jing Tan
Minjian Chen
Xihai Liu
Jianheng Ye
Shanghua Cai
Shanghua Cai
Yulin Deng
Jinchuang Li
Huichan He
Xin Zhang
Weide Zhong
Weide Zhong
Weide Zhong
Weide Zhong
Weide Zhong
author_sort Hongxiang Liu
collection DOAJ
description BackgroundClear cell renal cell carcinoma (ccRCC) is a malignant disease containing tumor-infiltrating lymphocytes. Reactive oxygen species (ROS) are present in the tumor microenvironment and are strongly associated with cancer development. Nevertheless, the role of ROS-related genes in ccRCC remains unclear.MethodsWe describe the expression patterns of ROS-related genes in ccRCC from The Cancer Genome Atlas and their alterations in genetics and transcription. An ROS-related gene signature was constructed and verified in three datasets and immunohistochemical staining (IHC) analysis. The immune characteristics of the two risk groups divided by the signature were clarified. The sensitivity to immunotherapy and targeted therapy was investigated.ResultsOur signature was constructed on the basis of glutamate-cysteine ligase modifier subunit (GCLM), interaction protein for cytohesin exchange factors 1 (ICEF1), methionine sulfoxide reductase A (MsrA), and strawberry notch homolog 2 (SBNO2) genes. More importantly, protein expression levels of GCLM, MsrA, and SBNO2 were detected by IHC in our own ccRCC samples. The high-risk group of patients with ccRCC suffered lower overall survival rates. As an independent predictor of prognosis, our signature exhibited a strong association with clinicopathological features. An accurate nomogram for improving the clinical applicability of our signature was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the signature was closely related to immune response, immune activation, and immune pathways. The comprehensive results revealed that the high-risk group was associated with high infiltration of regulatory T cells and CD8+ T cells and more benefited from targeted therapy. In addition, immunotherapy had better therapeutic effects in the high-risk group.ConclusionOur signature paved the way for assessing prognosis and developing more effective strategies of immunotherapy and targeted therapy in ccRCC.
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spelling doaj.art-f45e4641bc9146c2a6ca7a4ee9a0077b2023-07-11T16:42:12ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-07-011310.3389/fonc.2023.12021511202151A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinomaHongxiang Liu0Hongxiang Liu1Yong Luo2Shankun Zhao3Jing Tan4Minjian Chen5Xihai Liu6Jianheng Ye7Shanghua Cai8Shanghua Cai9Yulin Deng10Jinchuang Li11Huichan He12Xin Zhang13Weide Zhong14Weide Zhong15Weide Zhong16Weide Zhong17Weide Zhong18School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Urology, The First People’s Hospital of Zhaoqing, Zhaoqing, ChinaDepartment of Urology, The Second People’s Hospital of Foshan, Affiliated Foshan Hospital of Southern Medical University, Foshan, ChinaDepartment of Urology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, ChinaDepartment of Pediatrics, The First People’s Hospital of Zhaoqing, Zhaoqing, ChinaDepartment of Urology, The First People’s Hospital of Zhaoqing, Zhaoqing, ChinaDepartment of Urology, The First People’s Hospital of Zhaoqing, Zhaoqing, ChinaDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaUrology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Medical University, Guangzhou Laboratory, Guangzhou, ChinaUrology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaGuangzhou Medical University, Guangzhou Laboratory, Guangzhou, ChinaDepartment of Pathology, The Second People’s Hospital of Foshan, Affiliated Foshan Hospital of Southern Medical University, Foshan, ChinaSchool of Medicine, Jinan University, Guangzhou, ChinaDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaUrology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Medical University, Guangzhou Laboratory, Guangzhou, China0Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, Macao SAR, ChinaBackgroundClear cell renal cell carcinoma (ccRCC) is a malignant disease containing tumor-infiltrating lymphocytes. Reactive oxygen species (ROS) are present in the tumor microenvironment and are strongly associated with cancer development. Nevertheless, the role of ROS-related genes in ccRCC remains unclear.MethodsWe describe the expression patterns of ROS-related genes in ccRCC from The Cancer Genome Atlas and their alterations in genetics and transcription. An ROS-related gene signature was constructed and verified in three datasets and immunohistochemical staining (IHC) analysis. The immune characteristics of the two risk groups divided by the signature were clarified. The sensitivity to immunotherapy and targeted therapy was investigated.ResultsOur signature was constructed on the basis of glutamate-cysteine ligase modifier subunit (GCLM), interaction protein for cytohesin exchange factors 1 (ICEF1), methionine sulfoxide reductase A (MsrA), and strawberry notch homolog 2 (SBNO2) genes. More importantly, protein expression levels of GCLM, MsrA, and SBNO2 were detected by IHC in our own ccRCC samples. The high-risk group of patients with ccRCC suffered lower overall survival rates. As an independent predictor of prognosis, our signature exhibited a strong association with clinicopathological features. An accurate nomogram for improving the clinical applicability of our signature was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the signature was closely related to immune response, immune activation, and immune pathways. The comprehensive results revealed that the high-risk group was associated with high infiltration of regulatory T cells and CD8+ T cells and more benefited from targeted therapy. In addition, immunotherapy had better therapeutic effects in the high-risk group.ConclusionOur signature paved the way for assessing prognosis and developing more effective strategies of immunotherapy and targeted therapy in ccRCC.https://www.frontiersin.org/articles/10.3389/fonc.2023.1202151/fullclear cell renal cell carcinomareactive oxygen speciesprognosisimmune infiltratesimmunotherapy
spellingShingle Hongxiang Liu
Hongxiang Liu
Yong Luo
Shankun Zhao
Jing Tan
Minjian Chen
Xihai Liu
Jianheng Ye
Shanghua Cai
Shanghua Cai
Yulin Deng
Jinchuang Li
Huichan He
Xin Zhang
Weide Zhong
Weide Zhong
Weide Zhong
Weide Zhong
Weide Zhong
A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma
Frontiers in Oncology
clear cell renal cell carcinoma
reactive oxygen species
prognosis
immune infiltrates
immunotherapy
title A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma
title_full A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma
title_fullStr A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma
title_full_unstemmed A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma
title_short A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma
title_sort reactive oxygen species related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma
topic clear cell renal cell carcinoma
reactive oxygen species
prognosis
immune infiltrates
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fonc.2023.1202151/full
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